A New âSpinâ on Integrating NMR Spectroscopy into a Chemistry

Chapter 9

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A New “Spin” on Integrating NMR Spectroscopy into a Chemistry Curriculum Kate J. Graham, Edward J. McIntee,* and Chris P. Schaller Chemistry Department, College of Saint Benedict/Saint John’s University, 37 South College Avenue, St. Joseph, Minnesota 56374, United States *E-mail: [email protected]

The College of Saint Benedict/St John’s University (CSB/SJU) Chemistry Department has developed a foundation-level laboratory curriculum that emphasizes the development of practical skills. Given the prevalent use of NMR techniques across chemistry, significant emphasis in the curriculum was placed on building skills in the interpretation of NMR spectra. In the first introductory laboratory course, an incremental approach is used in which students encounter new aspects of spectroscopy each week. In subsequent courses, students are provided with opportunities to practice previously-learned skills, while new types of analysis are included periodically to build their repertoire.

The recent revision of undergraduate curricular guidelines from the American Chemical Society Committee on Professional Training (ACS-CPT) has generated interest in examining new ways of organizing course sequences both for chemistry majors and for non-majors. With NSF funding, The College of Saint Benedict/Saint John’s University (CSB/SJU) Chemistry Department has implemented a radical reconstruction of the foundation-level chemistry curriculum. A recent paper in Journal of Chemical Education outlines the way in which content has been reorganized into three sequences: structure, reactivity, and quantitation (1). The curriculum has been restructured to prepare students for learning and practicing modern science with a new set of courses (Figure 1). The removal of traditional disciplinary boundaries highlights the inter-relatedness of the chemical disciplines. © 2016 American Chemical Society

Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: Upper-Level Courses and Across the Curriculum Volume 3 ... ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Figure 1. CSB/SJU Curriculum Overview. (Reproduced with permission from reference (1). Copyright 2014, ACS Publications.) The CSB/SJU chemistry laboratory courses are formally separate from classroom courses. This arrangement has the advantage of freeing the laboratory from an illustrative or proof-of-concept role. The laboratory curriculum instead focuses on skill development and data analysis, preparing students for practical work or research. Project-based labs are employed, allowing students to work individually and exercise some choice over the order in which they do experiments, encouraging a general sense of laboratory independence (2–4). In addition, the practice of not repeating laboratories that students may have seen in high school allows all students an equal chance to succeed. NMR analysis has become an increasingly important technique across chemistry. Applications include structural, thermodynamic and kinetic studies involving organic synthesis, natural products isolation, polymer analysis, inorganic synthesis, biomacromolecules and other modern research areas. Due to the fact that NMR spectroscopy is critical in many modern chemistry projects, NMR spectral analysis has been integrated into every level of the CSB/SJU chemistry curriculum including foundation laboratories, integrated laboratory, in-depth courses and senior capstone research projects. The goal of this approach is to maximize student exposure to NMR spectroscopy, so that students can become more adept with the technique through multiple exposures. 146



Many articles in the chemical education literature have focused on the benefits of introducing chemistry students to modern scientific instrumentation early in their chemistry curriculum (5–14). A key piece of the CSB/SJU reorganized chemistry curriculum involves the introduction of spectroscopic techniques in the first several foundation laboratory courses. This approach allows ample exposure to NMR spectroscopic analysis over an undergraduate career and provides students with needed skills for early entry into research. The use of an autosampler and the ability to post FID files to a server for independent analysis by students were critical components for successful implementation in a larger introductory course. A detailed discussion of the implementation of NMR spectral analysis in the CSB/SJU curriculum is provided in the following sections. Finally, some assessment data are provided.

Foundation Lab: Purification and Separation Laboratory 1 Students are introduced to 1H and 13C NMR spectroscopic analysis during their first college laboratory course in chemistry, Purification and Separation Laboratory 1 (Purification 1). In Purification 1, students develop practical skills in the laboratory to prepare them to carry out tasks that chemists routinely do in research projects, such as the benchtop purification and identification of compounds. Students perform a range of purification techniques that build on their knowledge of basic laboratory skills: sublimation, distillation, recrystallization, solvent partitioning, and acid−base extraction (15–19). In each case, students must work independently to isolate a compound from an unknown sample. Students also work on learning to process their data and interpret the spectra for their purified compounds. For the report, students must develop an argument about the identity of the sample and its purity based on the spectral data that they obtain. In this foundation laboratory, first year students are introduced to spectral analysis while simultaneously using spectroscopic techniques. The laboratory is a three-hour experience. CSB/SJU uses a supplemental weekly one-hour recitation period to develop interpretation skills while students are simultaneously using spectroscopic techniques in the laboratory. Students are introduced to spectral interpretation through a guided inquiry process that has become a popular approach for the introduction of this material (20–25). In order to prepare students for this work, they are first taught to decipher line drawings of organic molecules. Students are led to develop rules for representing molecules as line drawings and to learn the names of functional groups. Infrared spectroscopy is the first spectroscopic technique introduced in recitation. Hooke’s law is discussed using an interactive lecture format along with small student led group presentations of molecular motions discovered by students by modeling selected compounds on Spartan (26). An interactive lecture using presentations and examples of infrared spectra along with in-class practice problems allow the students to build their own infrared spectral chart while reinforcing familiarity with the names of functional groups. 147


Concepts of molecular symmetry and chemical shift are introduced using Students use molecular models and an interactive lecture. The concept of chemical shift is simplified to a combination of carbon hybridization and electron withdrawing group effects. No detailed explanation of the theory of NMR spectroscopy is presented in this laboratory course. Integration and multiplicity are introduced through more interactive lecture with additional practice. The students apply their knowledge by processing, interpreting and determining the relative composition of a 1H-NMR sample containing toluene and an unknown. In this laboratory, students use IR and 1H-NMR to decide between unknowns of acetonitrile, dichoromethane, dimethyl sulfoxide, ethanol, ethyl acetate, methyl tert-butyl ether, pyridine, 2-propanol, and tetrahydrofuran. The unknown samples are spiked with approximately 20% toluene. Touene was chosen because the chemical shift of the methyl singlet is unique to the selected unknowns. Students then calculate the relative composition of the sample based on integration of a signal belonging to toluene and a signal belonging to their unknown (27). In recitation, students continue to work on solving spectral problems including their own lab spectral problems. Once the foundations for spectral interpretation are covered, students begin work on a variety of separation projects in any order they choose: sublimation, distillation, recrystallization, solvent partitioning, and acid−base extraction. All the projects except recrystallization rely on NMR spectral analysis to determine the student’s unknown. Students are graded mainly on data acquisition and interpretation. Minimal points (approximately 5% of report grade) are assigned to the correct identification of the unknown; instead students are evaluated on their spectral interpretation tables and laboratory process. Faculty also grade the quality of separation, the percent recovery, and an experimental section written utilizing a Journal of Organic Chemistry format. One of the first projects that students usually choose is distillation. In the distillation project, students separate an unknown from 1-hexanol and utilize 13CNMR, IR and gas chromatography (GC). Unknowns used in this lab are butyl acetate; ethyl acetate; cyclohexane; toluene; heptane; 2-butanone; 2-pentanone; 2-hexanol; 1-pentanol; 2-butanol; 2-propanol; 1-bromobutane; 1-bromopentane; pentanaldehyde; and tert-butyl bromide. Students often have some 1-hexanol impurity left in their sample and must report the percent composition of their purified sample as determined via GC. Solvent partitioning is a project in which students separate a polar impurity, glucose, from a relatively nonpolar compound using tert-butyl methyl ether to extract the unknown. Possible unknowns for this project are 9-fluorenone; benzophenone; 2-nitrobenzaldehyde; 3-nitrobenzaldehyde; 4-nitrobenzaldehyde; 2-indanone; 4-phenylcyclohexanone; 9-fluorenemethanol; 1-naphthalenemethanol; 4-biphenylmethanol; 2-indanol; 2-acetonaphthone; benzil; benzoquinone; 1-indanone; 1,4-dimethoxybenzene; trans-stilbene; and phenacetin. Students utilize 1H-NMR, IR and melting point analysis to determine their unknown and purity. In the sublimination project, students separate their unknown from a benzanilide contaminant. Potential unknowns that the students have to choose from are naphthalene; caffeine; camphor; anthracene; menthol; 1-


13C-NMR.

148 Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: Upper-Level Courses and Across the Curriculum Volume 3 ... ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


(ferrocenyl)ethanol; ferrocene; acetylferrocene; diacetylferrocene; trans-cinnamic acid; benzoic acid; and triphenylborane. Students utilize a setup composed of an erlenmeyer flask with an ice filled test tube as the cold finger to condense vapors (27). Students utilize 1H-NMR, IR and melting point analysis to determine their unknown and purity. Students often still have some benzanilide contaminant that they must identify. Often the last project that students do in Purification 1, is the acid-base extraction project. Students are told for which general scenario they will need to prepare. The possible scenarios are separation of a strong acid and a weak acid; a base and a neutral compound; an acid and a neutral compound; and an acid and a basic compound. Acids used in this project are salicylic acid; 2-chlorobenzoic acid; 2-methylbenzoic acid; benzoic acid; 1-naphthol; 4-methoxyphenol; and para-cresol. Basic compounds used in this project are 3-nitroaniline; 2-methyl-4-nitroaniline; 4-nitroaniline; and p-toludine. Neutral compounds used in this project are 1,4-dimethoxybenzene; anthracene; methyl benzoate; fluorine; 9-fluorenone; and trans-stilbene. A few other “red herring” compounds are listed in the laboratory manual along with those that are utilized. Weekly online multiple choice quizzes (~20% of the laboratory course grade) are used to reinforce concepts and hold students accountable for learning information in a timely fashion. In addition to classroom resources, online resources have also been developed to reinforce concepts discussed and practiced in the laboratory (28–31). Finally, students are evaluated by an online final exam of 34 spectroscopy-related questions comprised of items provided by the ACS Exams Institute. As reported in Table 1, CSB/SJU first semester students performed slightly above the national average. Most of the exam questions came from exams that would normally be taken by fourth semester (organic) or higher (biochemistry) students at other institutions.

Table 1. ACS Exam Data from Purification 1 Purification 1 AY 2015 Students (N)

236

Overall ACS Exam Average (%)

61

ACS Exam Subset National Data Average (%)

54

Foundation Lab: Purification and Separation Laboratory 2 In Purification and Chromatography Laboratory 2 (Purification 2), the format is similar to that of Purification 1. However, instead of having a separate recitation section, the laboratory sections are four hours long. Students develop and review spectral analysis skills and learn practical chromatographic purification skills in the laboratory. The first two weeks of lab involve recitations that include introductions to ultraviolet−visible (UV-vis) and mass spectrometry (MS) as well as further practice on NMR spectroscopic analyses. In the purification projects, 149 Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: Upper-Level Courses and Across the Curriculum Volume 3 ... ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


students perform chromatography experiments utilizing different separation methods including silica thin layer chromatography as well as columns with silica gel, ion exchange resin, reverse phase packing, size exclusion gel, and protein affinity gels. Additional characterization in the latter experiment is obtained by running a polyacrylamide gel electrophoresis experiment (PAGE). Students analyze their compounds utilizing MS and UV as well as the previously introduced NMR and IR techniques. Only some of these experiments entail analysis by NMR spectroscopy; specifically, there are two experiments that use column chromatography on silica, one that uses reverse phase chromatography, and one that utilizes size exclusion. Of the experiments involving silica chromatography, one involves the development of an eluent via TLC for the subsequent separation of an alcohol from a ketone or aldehyde (32, 33). An additional experiment uses the same technique to purify the products of an enzymatic chiral resolution (34). Students also separate a small peptide from a protein via size exclusion chromatography (35). Finally, the reverse phase column is used to separate an unknown polar compound from a contaminant of benzophenone (36). In the silica gel column chromatography project, students must determine an acceptable solvent ratio of hexanes and ethyl acetate to separate an alcohol from a ketone. Alcohols used for this project are 4-biphenylmethanol; 1-naphthalenemethanol; 9-fluorenemethanol; 2-indanol; 9-anthracenemethanol; and 2,2′-biphenyldimethanol. Ketones used for this project are 1-indanone; 1,4-benzoquinone; 9-fluorenone; 1,4-naphthoquinone; 2′-acetonaphthone; and 4-phenylcyclohexanone. Benzil is listed in the laboratory manual, but it is a red herring. Because students are using UV to visualize their compounds on TLC, all compounds needed to contain an aromatic ring. Students characterize both the alcohol and ketone unknowns by IR, melting point, and 1H-NMR analysis (32, 33). Students use the same type of methodology to separate the enzymatic products of a reaction of a racemic alcohol with an acyl donor. Racemic aromatic alcohols are reacted with a lipase and either vinyl propionate or vinyl acetate to yield an aromatic ester and an unreacted alcohol. Racemic alcohols utilized in this project are 1-phenylethanol; 1-phenyl-1-proanol; 1-phenyl-1-butanol; 1-phenyl-2-propanol; and α-methyl-2-naphthalenemethanol. Students use UV to visualize their compounds on TLC and separate by using silica gel chromatography. Students determine what their starting alcohol was and the ester product via IR, 1H-NMR and 13C-NMR. Students also determine the stereoselectivity of this reaction by determining the optical purity of their remaining alcohol (34). Students are introduced to the 1H-NMR implications of compounds having diastereotopic protons in the size exclusion project. In this project, students use a P-4 size exclusion gel to separate a small peptide or amino acid methyl ester from a protein, bovine serum albumin. Blue Dextran is spiked into the mixture so students can more easily identify fractions that contain their protein. Fraction sizes of approximately 200 microliters are collected into 96-well acrylic plates and analyzed on a plate reader. Students collect and dry the fractions containing their peptide. Peptides used in this project are Phe-Ala; Phe-Val; Phe-Leu; 150



phenylalanine methyl ester; and tryptophan methyl ester. Students determine which peptide they have by comparison to standard retention times and mass spectral pattern via GC-MS. In addition, students confirm their structure by 1H-NMR analysis (35). The last project in Purification 2, is the separation of a phenolic or carboxylic compound from a benzophenone contaminant using C-18 solid phase extraction. Phenolic and carboxylic acids used in this project are gallic acid; salicylic acid; tyrosol; trans-cinnamic acid; benzoic acid; umbelliferone; para amino benzoic acid; phenylalanine methyl ester; and tryptophan methyl ester. Students determine the structure of their unknown via IR, GC-MS, 1H-NMR and 13C-NMR (37). During the first several weeks of the course, students are assigned spectral problems containing UV, MS, 1H-NMR and 13C-NMR data. In the third week of the course, students are given an online quiz of 20 multiple choice spectral interpretation questions. Finally, students are evaluated by an online final of 54 questions comprised of 10 in-house questions and 44 questions provided by the ACS Exams Institute. As seen in Table 2, CSB/SJU second semester students performed slightly above the national average.

Table 2. Final Exam Data from Purification 2 Purification 2 AY 2015 Students (N)

179

Overall ACS Exam Average (%)

62

ACS Exam Subset National Data Average (%)

55

Foundation Lab: Synthesis Laboratory In the synthesis laboratory course, students work on projects to develop practical synthetic skills including the reduction of a carbonyl compound, a carboxylic substitution reaction, ring-opening polymerization, synthesis of a coordination complex, synthesis of nanoparticles, formation of a fluorescently labeled liposome, and expression of a fluorescent protein. Additional aspects of NMR spectral determination such as 2D techniques (37), 31P-NMR spectroscopy and polymer end group analysis are added to the course content. NMR spectroscopy is used to analyze the products of a reduction reaction. Students are given an unknown, either an aldehyde, anhydride, ketone, amide, acid or nitrile that they reduce with lithium aluminum hydride. Students practice using moisture sensitive techniques by running the reaction under nitrogen. Lithium aluminum hydride is a strong reducing agent and used to ensure that the reactions mostly go to completion so that no further purification other than simple extraction is necessary. Unknowns used in this project are benzaldehyde; 2-furfural; acetophenone; phenylethanal; trans-cinnamaldehyde; trans-cinnamic acid; 3-phenylpropionaldehyde; phthalic anhydride; phthalide; 2-cyclohexen-1-one; acetanilide; 9-acetylanthracene; benzophenone; benzonitrile; 4-tert-butyl 151



cyclohexanone; 4-phenylcyclohexanone; 9,10-anthraquinone; and citronellal. Students obtain IR, 1H-NMR and COSY to characterize their product. Students also report on percent composition of their sample. Students also utilize NMR to analyze starting materials and products of a carboxylic substitution reaction. Students are assigned an electrophile, either benzoyl chloride or acetyl chloride, and given an unknown alcohol or amine. Alcohol unknowns for this project are benzyl alcohol; cyclohexanol; 1-butanol; 1-octanol; 1-decanol; cinnamyl alcohol; allyl alcohol; and 2-butanol; 2-octanol. Amine unknowns for this project are 2-butylamine; 2-propylamine; allylamine; benzylamine; ethylamine; cyclohexylamine; cinnamylamine; 1-butylamine; 1-octylamine; and 1-decylamine. Students obtain IR, 1H-NMR, and 13C-NMR on their unknown nucleophile and IR, 1H-NMR, 13C-NMR, and HMQC of their product. In synthesis lab, students also analyze the product of a ring-opening polymerization to determine the approximate number of monomers that reacted. Students are assigned a lactone, an initiator, and a catalyst. Lactone compounds used for this project are L-lactide; D-lactide; racemic-lactide; δ-valerolactone; and ε-caprolactone. Initiators are either 2-phenylethanol, used for the lactides, or benzyl alcohol, used for the other lactones. Octoate or zinc acetylacetonate are used to catalyze the polymerization. Students obtain a 1H-NMR and examine the relative integral ratios in the aromatic region with selected signals in the aliphatic region to determine the number of monomeric units incorporated into their polymer. The synthesis of a transition metal phosphine complex provides an opportunity to use 31P-NMR spectroscopy. Results are compared against a table of shifts for the free ligands. Students use their spectra to confirm that the ligand is coordinated to the metal and free of excess phosphine. Starting metallic complexes for this project are nickel (II) chloride hexahydrate; bromo pentacarbonyl manganese; and molybdenum hexacarbonyl. The phosphine containing ligands that are used are bis(diphenylphosphino)methane; 1,2-bis(diphenylphosphino)ethane; and 1,2-bis(diphenylphosphino)propane. Students obtain IR, 1H-NMR and 31P-NMR to characterize the products. These experiments are used to introduce 2D NMR spectroscopy in relatively simple compounds, with a COSY for the carbonyl reduction and HMQC for the carboxylic substitution reaction. 2D spectroscopy is not crucial for the confirmation of the structures of these compounds, but the exercise provides a simple case in which students can correlate information along both axes with their structure. The laboratory experiment is augmented by practice problems that illustrate COSY and HMQC. Initial examples demonstrate the techniques using very simple molecules and slowly building to typical small organic compounds that students will encounter in their synthesis projects. As a capstone synthesis project in this course, students also work with a partner to choose a reaction procedure to follow from the literature and modify the procedure to be more environmentally benign (38). NMR spectroscopic analysis is required for this experiment for students to determine their success. Most students choose the most familiar methods, 13C and 1H NMR spectroscopy. 152



In general, performance on spectroscopy has not been assessed separately in Synthesis Laboratory. Spectroscopic analysis also influences grades on laboratory reports. During this upcoming year, a separate, individualized assignment on structure elucidation via IR and NMR spectroscopy and mass spectrometry will be introduced during the third week of laboratory. After these foundational laboratory experiences, chemistry majors continue on to an Integrated Laboratory while biochemistry majors, chemistry minors and premedical students take only the foundation laboratories in this sequence. Currently, biology majors take the two Purification laboratories, proceeding further only if interested in pre-health professions.

Integrated Laboratory After an introduction to electronics, students work on computational chemistry with organic, inorganic, and biochemical structures, perform enzyme kinetics and examine protein−substrate interactions, investigate metal binding to deoxyribonucleic acid (DNA) and metal-catalyzed alkene isomerization, analyze the products of the photolysis of pharmaceuticals, and perform an experiment with a Schlenk line. Students also plan and carry out a three-step organic synthesis (39). These experiments are supported by a variety of analyses, including NMR (both 1D and 2D), IR, UV−vis and fluorescence spectroscopy, mass spectrometry, cyclic voltammetry, magnetic susceptibility, GC, and high-performance liquid chromatography (HPLC). In this laboratory, students are required to analyze the products of their organic synthesis project via NMR spectroscopy. Additionally, a coordination compound is also subjected to kinetic analysis using data obtained via 1H NMR spectroscopy (40). NMR spectroscopy has not been directly assessed in integrated laboratory, although skill with the technique is presumed to be a necessary requirement for high performance on the organic synthesis project. During the 2015-16 academic year, an organic spectroscopy quiz will be introduced prior to the organic synthesis project.

In-Depth Course: Structure Elucidation In the last fifteen years, the number of laboratory experiments incorporating 2D NMR analysis has exploded in chemical literature. Familiarity with spectral analysis is essential for chemists in many areas, such as medicinal chemistry, process chemistry, natural products chemistry, polymer chemistry, forensic chemistry, and many other sub-specialties of analytical chemistry. Many chemistry graduates will need extensive experience in structure determination using a variety of NMR spectroscopic techniques. The basic principles of NMR and the use of different techniques such as decoupling, relaxation time measurements, NOE, and interpretation of 1D and 2D NMR spectra are covered in this in-depth course for chemistry majors. The major emphasis of this course is on molecular structure determination and provides 153


students with ample practice on interpretation. Similar courses have been taught at either advanced undergraduate or graduate level (41). It is important to remember that solving spectral problems is not something that can be learned from simply reading; practice in interpreting spectra is mandatory. For the purposes of this course, a spectral problem database including many 2D NMR problems is being developed at CSB/SJU (42).


Introduction to Research and Capstone Research If students are interested in research, they have the opportunity to take an introductory ‘research bootcamp’ course intended for second and third year students. Student teams are paired with faculty mentors and given mini-research projects that can range from a laboratory development project to synthesis of key intermediates for other projects to development of new synthetic methodologies. In this introduction to research course, many students choose projects that require compound characterization. Introduction of students to spectral techniques early in our curriculum is essential for their success in this course. Majors in their fourth year must complete a Capstone Research project. Students are paired with a faculty mentor. Typically, matching a faculty mentor and a research student occurs in the spring of their third year. For the capstone, students work in the laboratory for a minimum of four hours a week for the entire academic year. They are required to do background literature searches on their laboratory project along with an oral presentation of what they accomplished in the laboratory. Students also write an ACS style research paper on their work. Many of the capstone projects involve characterization of compounds and materials via NMR.

Assessment In the spring of 2015, the CSB/SJU Chemistry department graduated its first cohort of students that completed this curriculum. Data on some courses are limited to the past four years or fewer. In the first two laboratory courses (Purification 1 and 2), students are administered a final exam that is comprised of either a mixture of questions developed at CSB/SJU and questions provided by the ACS Exams Institute or simply questions provided by the ACS Exams Institute. Academic year 2015 was the first year that this exam was administered. As shown in Table 1 (vide supra), first semester students at CSB/SJU performed slightly above the average difficulty index for these questions reported nationally. The same trend can be seen with the data for second semester CSB/SJU students, shown in Table 2. Students on both exams performed well in questions dealing with IR and 1H-NMR spectroscopies, Solubility, and Hydrogen bonding – Intermolecular Forces. These results are promising, given that the exam questions came from examination forms that would normally be taken by more mature students at other institutions. No formal assessment was given in the synthesis or integrated laboratories. However, two forms of senior exit exams were administered in 2015, the Major 154



Field Test (MFT) in Chemistry and the ACS Standardized Exam: Diagnostic of Undergraduate Chemistry Knowledge (DUCK). A line item analysis for the MFT is not available. However, the DUCK exam does provide a line item analysis. In the spring of 2015, 14 CSB/SJU students took the DUCK exam. The question on the DUCK that dealt with 1H-NMR spectroscopy, 72% CSB/SJU students answered correctly. The ACS subset national data average for this question was 69%. Similarly, 79% of CSB/SJU students answered the question on 13C-NMR correctly, while the ACS subset national data average for this question was 73%. The MFT has been administered by our department since 2005. As is shown in Table 3, although our sample size of students taking the MFT exam in 2015 was small (N = 13), the results are similar to results seen from pre-curricular changes.

Table 3. Major Field Test Data CSB/SJU Academic Year

N

Analytical

Inorganic

Organic

Physical

Biochemistry

2015

13

74

83

92

69

70

2014*

17

92

94

75

81

71

2013*

22

83

84

76

82

84

2005-12

125

78

77

73

71

85

* students taking the MFT in these years were exposed to a hybrid

N = number of students. of our curriculum as we taught out the old curriculum.

Conclusions Students at CSB/SJU are introduced to NMR spectroscopy and other spectroscopic methods at an early stage in the laboratory setting. This laboratory experience is not tied to any lecture course, and so instructors teach an understanding of spectroscopy completely within the lab course. In the first semester laboratory (Purification 1), students are introduced to IR, 13C- and 1H-NMR along with separations techniques. Purification 1 is a three-hour laboratory experience supported by a one-hour recitation. Spectroscopic interpretation skills are reinforced in the second semester laboratory course (Purification 2). Purification 2 is a laboratory course built around chromatographic separations. New methods of structural data interpretation, UV and MS, are introduced at this point. Two-dimensional and multinuclear NMR are introduced in the third semester course (Synthesis). All spectroscopic techniques are reinforced in Integrated Lab. Additional 2D and 3D NMR methods are introduced in in-depth course offerings. Finally, students apply much of what they have learned and decide on appropriate characterization techniques in our Introduction to Research and Capstone Research courses. The Chemistry department graduated its first cohort of students that have completed this curriculum in the spring of 2015. There has been an increase in the numbers of graduating biochemistry and chemistry majors between 2011 (24 majors graduated), when implementation of 155


the new curriculum began, and 2015 (43 majors graduated). Assessment data suggests that CSB/SJU graduates are performing similarly to peers nationally on spectroscopy problems.


Future Goals and Considerations CSB/SJU students in the new curriculum have performed well compared to peers nationally based on a number of assessment tools, but there are still areas for improvement. In the upcoming year students in the synthesis laboratory will be given more practice problems involving 1D and 2D NMR spectroscopy. In addition, a final exam similar to those in the Purification 1 and 2 laboratories is planned. In the upcoming year, students in the integrated laboratory will be given an assessment on their spectral interpretation skills. Students needing more practice in certain areas, such as pattern recognition or chemical shift, will be directed to additional spectral problems for practice. The assessment will take place prior to students doing any experiments in the ‘synthesis module’ of the course. Integrated laboratory projects change every year, but many of the projects planned for the next several years will involve advanced NMR techniques; there are many examples in the chemical literature (43–49). Additional multinuclear experiments will also be included. For instance, a laboratory centered on screening inhibitors for the enzyme uridine nucleoside ribohydrolase found in Trichomonas vaginalis via 19F-NMR is also being considered (50). In addition, a comprehensive final is planned for the integrated laboratory course.

Acknowledgments The authors would like to thank the National Science Foundation for providing funds for our transformative curriculum (DUE-1043566) and for the purchase of a 400 MHz NMR (MRI-0922691). In addition, we would like to thank T. Nicholas Jones for gathering assessment data on our curriculum.

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